Clinical Trials /

Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

NCT02048020

Description:

This phase II trial studies how well paclitaxel and carboplatin before radiation therapy with paclitaxel works in treating human papillomavirus (HPV)-positive patients with stage III-IV oropharynx, hypopharynx, or larynx cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving paclitaxel and carboplatin before radiation therapy with paclitaxel may kill more tumor cells.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Paclitaxel</span> and <span class="go-doc-concept go-doc-intervention">Carboplatin</span> Before <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy With <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer

Title

  • Brief Title: Paclitaxel and Carboplatin Before Radiation Therapy With Paclitaxel in Treating HPV-Positive Patients With Stage III-IV Oropharynx, Hypopharynx, or Larynx Cancer
  • Official Title: Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV)
  • Clinical Trial IDs

    NCT ID: NCT02048020

    ORG ID: 13-000915

    NCI ID: NCI-2013-02394

    Trial Conditions

    Human Papilloma Virus Infection

    Stage III Squamous Cell Carcinoma of the Hypopharynx

    Stage III Squamous Cell Carcinoma of the Larynx

    Stage III Squamous Cell Carcinoma of the Oropharynx

    Stage III Verrucous Carcinoma of the Larynx

    Stage IV Squamous Cell Carcinoma of the Hypopharynx

    Stage IV Verrucous Carcinoma of the Larynx

    Stage IVA Squamous Cell Carcinoma of the Larynx

    Stage IVA Squamous Cell Carcinoma of the Oropharynx

    Stage IVA Verrucous Carcinoma of the Larynx

    Stage IVB Squamous Cell Carcinoma of the Larynx

    Stage IVB Squamous Cell Carcinoma of the Oropharynx

    Stage IVB Verrucous Carcinoma of the Larynx

    Stage IVC Squamous Cell Carcinoma of the Larynx

    Stage IVC Squamous Cell Carcinoma of the Oropharynx

    Stage IVC Verrucous Carcinoma of the Larynx

    Trial Interventions

    Drug Synonyms Arms
    paclitaxel Anzatax, Asotax, TAX, Taxol Treatment (paclitaxel, carboplatin, IMRT)
    carboplatin Carboplat, CBDCA, JM-8, Paraplat, Paraplatin Treatment (paclitaxel, carboplatin, IMRT)

    Trial Purpose

    This phase II trial studies how well paclitaxel and carboplatin before radiation therapy
    with paclitaxel works in treating human papillomavirus (HPV)-positive patients with stage
    III-IV oropharynx, hypopharynx, or larynx cancer. Drugs used in chemotherapy, such as
    paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either
    by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x
    rays to kill tumor cells. Giving paclitaxel and carboplatin before radiation therapy with
    paclitaxel may kill more tumor cells.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the progression-free survival at 2 years in patients with HPV-positive head
    and neck squamous cell carcinoma (HNSCC) who receive induction chemotherapy followed by dose
    de-intensified chemoradiotherapy.

    SECONDARY OBJECTIVES:

    I. To determine the overall survival and local-regional control for patients with
    HPV-positive HNSCC who receive induction chemotherapy and dose de-intensified
    chemoradiotherapy.

    II. To determine the incidence of acute grade 3+ mucosal and esophageal toxicity associated
    with attenuated concurrent chemoradiotherapy in patients with HPV-positive HNSCC.

    III. To determine the incidence of late toxicity in patients with HPV-positive HNSCC who
    receive the dose de-intensified chemoradiotherapy.

    IV. To estimate the incidence of all toxicity (hematologic and non-hematologic) associated
    with protocol treatment for all patients on trial.

    V. To estimate the response rate of HPV-positive to induction chemotherapy using carboplatin
    and paclitaxel.

    VI. To determine the effect of reduced radiation dose on short-term and long-term quality of
    life among patients treated by chemoradiotherapy.

    OUTLINE:

    INDUCTION: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV
    over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of
    disease progression or unacceptable toxicity.

    CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients
    receive paclitaxel IV over 1 hour weekly and undergo intensity-modulated radiation therapy
    (IMRT) daily 5 days a week for 5.5 weeks in the absence of disease progression or
    unacceptable toxicity.

    After completion of study treatment, patients are followed up at 6, 9, and 12 months, every
    3 months for 1 year, and then every 6 months for 2 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (paclitaxel, carboplatin, IMRT) Experimental INDUCTION: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients receive paclitaxel IV over 1 hour weekly and undergo IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. paclitaxel, carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologically (histologically or cytologically) proven (from primary lesion and/or
    lymph nodes) diagnosis of HPV-positive squamous cell carcinoma of the oropharynx,
    hypopharynx, or larynx; HPV-positivity will be defined as tumors that are
    p16-positive by immunohistochemistry

    - Clinical stage III or IV disease; note: patients with M1 tumors are not eligible

    - Appropriate stage for protocol entry, including no distant metastases, based upon the
    following minimum diagnostic workup:

    - History/physical examination within 4 weeks prior to registration, including
    assessment of weight loss in past 6 months

    - Chest x-ray (or chest computed tomography [CT] scan or positron emission
    tomography [PET]/CT scan) within 6 weeks prior to registration

    - CT scan or magnetic resonance imaging (MRI) of the head and neck (of the primary
    tumor and neck nodes) and PET/CT scan

    - Zubrod performance status 0-1

    - Absolute neutrophil count (ANC) > 1,800 cells/mm^3

    - Platelets > 100,000 cells/mm^3

    - Hemoglobin (Hgb) > 8.0 g/dl (note: the use of transfusion or other intervention to
    achieve Hgb > 8.0 g/dl is acceptable)

    - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2x the upper
    limit of normal

    - Serum creatinine =< 1.5 mg/dl or institutional upper limit of normal

    - Creatinine clearance (CC) >= 50 ml/min determined by 24-hour collection or estimated
    by Cockcroft-Gault formula

    - Negative serum pregnancy test within 7 days prior to start of induction chemotherapy
    (ICT) for women of childbearing potential

    - Women of childbearing potential and male participants are counseled on birth control
    and must agree to use a medically effective means of birth control throughout their
    participation in the treatment phase of the study (until at least 60 days following
    the last study treatment)

    - Patient must sign study specific informed consent prior to study entry

    Exclusion Criteria:

    - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
    for a minimum of 3 years

    - Patients with simultaneous primaries or bilateral tumors are excluded

    - Patients who have had initial surgical treatment other than the diagnostic biopsy of
    the primary site or nodal sampling of the neck disease are excluded

    - Patients with unknown primary tumor sites are excluded

    - Patients who present with a cervical lymph node metastasis of unknown primary origin

    - Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
    different cancer is allowable

    - Prior radiotherapy that would result in overlap of radiation therapy fields

    - Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses,
    or salivary glands

    - Recurrent head and neck cancer

    - Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable
    angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive
    heart failure, and cardiomyopathy with decreased ejection fraction

    - Congestive heart failure with left ventricular ejection fraction < 20%

    - Transmural myocardial infarction within the last 6 months

    - Acute bacterial or fungal infection requiring intravenous antibiotics at registration

    - Chronic obstructive pulmonary disease exacerbation or other respiratory illness
    requiring hospitalization or precluding study therapy at the time of registration

    - Active lupus erythematosus or scleroderma with ongoing physical manifestations

    - Any uncontrolled condition, which in the opinion of the investigator, would interfere
    in the safe and timely completion of study procedures

    - Pregnant or lactating women or women of childbearing potential and men who are
    sexually active and not willing/able to use medically acceptable forms of
    contraception

    - Prior allergic reaction to the study drug(s) involved in this protocol

    - Patient is enrolled in another investigational trial

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival

    Secondary Outcome Measures

    Overall survival

    Local-regional control

    Incidence of mucosal and esophageal >= grade 3 toxicity graded according to the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0)

    Incidence of other >= grade 3 toxicity graded according to NCI CTCAE v4.0

    PTD

    Incidence of death

    Quality of life as assessed by Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) and University of Washington Quality of Life (UWQol)

    Trial Keywords